Search Results (12,769)

Recent studies have identified N6-methyladenosine (m6A) RNA methylation as a key regulatory mechanism in tumor progression. This study aimed to elucidate the biological function and clinical relevance of the m6A methyltransferase METTL3 in cutaneous T-cell lymphoma (CTCL). Our findings demonstrated that METTL3 expression is upregulated in CTCL, and its knockdown suppresses CTCL progression. Mechanistically, the downregulation of METTL3-mediated m6A modification on ARHGEF12 mRNA accelerated its degradation, a process that is closely associated with tumor behaviors. These results suggest that METTL3 may serve as a potential therapeutic target in CTCL. Full article

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with high metastatic potential, poor prognosis, and the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). The lack of these receptors limits the standard treatments, such as hormone therapies and HER2-targeted antibodies like trastuzumab. These challenges highlight the critical need for novel therapeutic strategies. CD147, a transmembrane glycoprotein overexpressed in TNBC, promotes tumor progression, metastasis, and chemoresistance, making it a promising therapeutic target. This study evaluates the antibody-dependent cellular cytotoxicity (ADCC) of HuM6-1B9, a humanized anti-CD147 antibody, against MDA-MB-231 cells, a TNBC model. Methods: CFSE-labelled MDA-MB-231 cells were co-cultured with PBMCs as effector cells (E:T ratio 80:1) in the presence of HuM6-1B9 and incubated for 4 h. Cells were then collected and stained with PI, and CFSE+/PI+ dead target cells were analyzed by flow cytometry. Results: Co-culturing MDA-MB-231 cells with peripheral blood mononuclear cells (PBMCs) in the presence of HuM6-1B9 demonstrated effective ADCC induction without direct cytotoxicity. HuM6-1B9 induced 54.01% cancer cell death via ADCC, significantly outperforming trastuzumab (26.14%) while sparing PBMCs. Conclusion: These findings support HuM6-1B9 as a prospective TNBC therapeutic and warrant further investigation into its clinical potential. Full article

Background: This study examined differences in body composition, dietary intake, and exercise habits between people with type 1 diabetes (T1DM) and those without diabetes (NDM). We also sought to clarify the clinical and lifestyle characteristics of overweight people with T1DM. Methods: This controlled cross-sectional study was conducted at a single center, and included 45 people with T1DM and 50 NDM individuals. Body composition, nutrient intake, and exercise habits were evaluated, and exercise habits were compared between people with a T1DM onset before 20 years of age and those with an onset at or after 20 years of age, in relation to the NDM group. Overweight was defined using a BMI of 25.0 kg/m² as the cutoff. Results: The T1DM group had significantly higher BMI and body fat than the NDM group, but no significant difference in muscle mass, and consumed a higher percentage of carbohydrates and a lower percentage of fat. The early-onset T1DM group had significantly lower exercise habits during their school years and in their current life than the NDM group. Individuals in the overweight T1DM group had a lower time in range on a continuous glucose monitor and a higher carbohydrate intake than those in the non-overweight T1DM group. Conclusions: The study suggested that the T1DM group had a significantly higher body fat percentage and carbohydrate intake, and significantly reduced exercise habits as students, compared to the NDM group. Full article

Background/Objectives: Antibiotic-associated diarrhea (AAD) is a public health problem that develops in the hospital setting. The most common causative agent of AAD is Clostridioides difficile infection (CDI), although other non-difficile Clostridia (NDC) might also be present. NDC include members of the RIC group such as Clostridium ramosum [T. ramosa], Clostridium innocuum and Clostridium clostridioforme [E. clostridioformis]. The co-colonization of NDC and CDI in patients with AAD has not been fully analyzed. Methods: We compared clinical and laboratory data of patients with C. difficile infection (CDI) plus NDC against patients with only CDI. This study was a retrospective, case–control study. Hospitalized confirmed CDI cases were analyzed. CDI detection was performed using a 2-step diagnostic algorithm, including glutamate dehydrogenase (GDH) with toxin A/toxin B assays and molecular detection of the tpi gene. Stool samples were cultured and colonies morphologically compatible with any Clostridia were identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fisher’s exact test and odds ratio (OR) were calculated to determine the degree of correlation between the variables and the study groups. Results: In the CDI + NDC group (n = 7), positive culture was observed for C. ramosum [T. ramosa] (n = 3), C. innocuum (n = 3), and C. butyricum (n = 1). According to our results, CDI + NDC patients received more days of antibiotic therapy, took more days to reduce diarrhea, had a significant increase in the number of days to suppress diarrhea, and previous hospitalizations were more frequently reported. Conclusions: In conclusion, the positive culture of NDC species such as C. innocuum or C. ramosum in patients with AAD caused by CDI correlates with treatment extension and/or failure. Full article

Objectives: The preoperative identification of occult pleural metastasis (OPM) in lung cancer remains a crucial clinical challenge. This study aimed to develop and validate a predictive model that integrates clinical information with chest CT radiomic features to preoperatively identify patients at risk of OPM. Methods: This study included 50 patients diagnosed with OPM during surgery as the positive training cohort and an equal number of nonmetastatic patients as the negative control cohort. Using least absolute shrinkage and selection operator (LASSO) logistic regression, we identified key radiomic features and calculated radiomic scores. A predictive nomogram was developed by combining clinical characteristics and radiomic scores, which was subsequently validated with data from an additional 545 patients across three medical centers. Results: Univariate and multivariate logistic regression analyses revealed that carcinoembryonic antigen (CEA), the neutrophil-to-lymphocyte ratio (NLR), the clinical T stage, and the tumor–pleural relationship were significant clinical predictors. The clinical model alone achieved an area under the curve (AUC) of 0.761. The optimal integrated model, which combined radiomic scores from the volume of interest (VOI) with the CEA and NLR, demonstrated an improved predictive performance, with AUCs of 0.890 in the training cohort and 0.855 in the validation cohort. Conclusions: Radiomic features derived from CT scans show significant promise in identifying patients with lung cancer at risk of OPM. The nomogram developed in this study, which integrates CEA, the NLR, and radiomic tumor area scores, enhances the precision of preoperative OPM prediction and provides a valuable tool for clinical decision-making. Full article

Background: Type 1 diabetes (T1D) and hidradenitis suppurativa (HS) share several metabolic and inflammatory dysfunctions. Prior studies of the potential link between the diseases either lacked validated T1D diagnoses or established only an indirect association. This study sought to determine the odds of HS developing in patients with a validated diagnosis of T1D and to characterize the clinical features of HS/T1D comorbidity. Methods: A population-based nested case-control study was conducted including patients with HS and controls matched 5:1 for age, sex, and primary care clinic. T1D was diagnosed using a specialized algorithm, achieving 90% accuracy. Diagnostic validity was confirmed by diabetes specialists who manually reviewed a random subset of the files. Unadjusted and adjusted odds ratios (OR/aOR) were calculated to determine the odds of incident HS in patients with T1D. Results: The study included 10,919 patients with HS and 53,314 controls. A history of T1D was associated with an elevated odds of new-onset HS (OR 1.80 95% CI (1.30–2.40), p < 0.001), even after adjusting for demographics and metabolic and autoimmune comorbidities (aORs > 1.7, p < 0.001). Patients with HS/T1D comorbidity had higher proportions of autoimmune conditions than patients with HS alone (p < 0.001) and a higher mean Charlson Comorbidity Index score than both patients with HS alone (3.5 vs. 0.9, p < 0.001) and T1D alone (3.5 vs. 2.2, p = 0.004). Conclusions: T1D is associated with higher odds of the subsequent development of HS. Awareness of HS/T1D comorbidity is recommended owing to the elevated burden of metabolic and autoimmune conditions. Full article

Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of hematological malignancies, demonstrating high efficacy in targeting and eliminating cancer cells. However, its clinical application can be associated with the risk of acute adverse effects, including cytokine release syndrome (CRS), a severe inflammatory response caused by excessive cytokine production. While anti-cytokine therapies are available to manage CRS, additional strategies are needed to optimize CAR T-cell efficacy with reduced toxicities. Curcumin, a bioactive polyphenol known for its anti-inflammatory and antioxidant properties, represents a promising adjunct for CAR T-cell therapy. In this study, we investigated the effects of curcumin on anti-CD19 CAR T-cells in vitro. Our results show that curcumin enhances the cytotoxic activity of CAR T-cells against Nalm-6, a B-cell acute lymphoblastic leukemia model, while reducing the production of pro-inflammatory cytokines, including IL-2 and IFN-γ. To explore its underlying mechanisms, network pharmacology and molecular docking analyses were performed, which revealed that curcumin interacts with key signaling pathways involved in T-cell activation and cytokine regulation. These findings support the potential of curcumin as a therapeutic adjunct to improve CAR T-cell efficacy while mitigating inflammatory toxicity. Full article

Coronavirus disease (COVID-19) exhibits a wide spectrum of clinical severity and has been associated with specific biomarkers linked to disease progression and outcomes. This retrospective study analyzed sera from 1222 adult COVID-19 patients hospitalized at the University Hospital for Infectious Diseases in Croatia. We examined the association between several laboratory biomarker levels measured at patient admission and disease severity, fatal outcomes, viral variants and clinical parameters. Deceased patients and surviving patients with severe COVID-19 exhibited significantly elevated levels of several biomarkers on admission, including hs-troponin T, N-terminal pro-brain natriuretic peptide, creatine kinase, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, lactate, urea and creatinine. Random forest models identified lymphocyte percentage, D-dimers, and hs-troponin T as the most important biomarkers for fatal outcome prediction, achieving 84.1% accuracy. Patients infected with the Delta SARS-CoV-2 variant exhibited significantly higher levels of proinflammatory, cardiac and renal biomarkers. Vaccination correlated with reduced proinflammatory parameters and higher lymphocyte proportions. Hypertension, chronic renal disease and diabetes were associated with increased cardiac, renal and metabolic biomarker levels, respectively. These findings highlight the association of several laboratory biomarkers with COVID-19 severity, viral variants, vaccination status and comorbidities, potentially offering prognostic insights into COVID-19 outcomes. Full article

Background/Objectives: The determination of glycated haemoglobin (HbA1c) is a cornerstone of the diagnosis and management of diabetes mellitus, serving as a reliable biomarker for assessing long-term glycaemic control. While high-performance liquid chromatography (HPLC) is regarded as the gold standard for HbA1c measurement, its widespread adoption is limited by high costs, operational complexity, and resource requirements. Alternative methodologies, including immunoturbidimetric assays, have garnered interest as practical solutions. This study evaluates the analytical performance of an immunoturbidimetric method for HbA1c determination and its comparability with a validated HPLC method. Methods: The evaluation process was conducted in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. The results from 178 human sample leftovers, covering the medical decision range, were compared with those obtained using the HPLC-based Menarini ADAMS A1c HA-8180T system. The analytical performance regarding repeatability and within-laboratory imprecision was also assessed. The probability risk of misinterpreting the analytical results was also calculated. Results: The Passing–Bablok regression indicated a strong correlation between the two methods, with a slope of 1.00 (95% CI: 1.00 to 1.04). The Bland–Altman analysis confirmed minimal systematic differences, showing a mean bias of −0.07% for NGSP and −0.74 mmol/mol for IFCC, both falling within the predefined total allowable error (ATE) limits. Imprecision studies demonstrated excellent repeatability and intermediate precision, with coefficients of variation (CV) ranging from 0.68% to 2.4% across all levels. The risk assessment of diagnostic misinterpretation indicated minimal deviation from an ideal analytical system, in which the measurement uncertainty was regarded as zero. Conclusions: The findings establish the immunoturbidimetric method as a reliable and cost-effective alternative to HPLC for routine HbA1c determination. Its strong analytical performance, combined with operational efficiency, makes it a valuable tool for laboratories, particularly in resource-limited settings, enhancing access to high-quality diabetes monitoring. Full article

Osteosarcoma is a highly aggressive bone malignancy, particularly challenging in metastatic cases, with a 5-year survival rate remaining under 30%. Although doxorubicin (doxo) is a standard first-line chemotherapeutic agent, its clinical utility is often hindered by the development of drug resistance and associated systemic toxicity. Emerging evidence highlights the role of epigenetic alterations, particularly those involving histone deacetylases (HDACs), in promoting chemoresistance. In this context, the present study aimed to evaluate the therapeutic potential of combining doxo with the selective HDAC inhibitors, tasquinimod (Tas, targeting HDAC4) and PCI-34051 (PCI, targeting HDAC8), in SJSA-1 osteosarcoma cells. Utilizing both 2D and 3D in vitro models, the combination treatment (referred to as the T4 group) significantly reduced cell viability by 57.69% in 2D cultures and decreased spheroid volume by 35.19% in 3D models. The apoptotic response was markedly enhanced, with late apoptosis reaching 64.59% and necrosis at 32.07%, both surpassing the effects observed with doxo alone. Furthermore, wound healing assays demonstrated a 37.74% inhibition of migration, accompanied by a decreased expression of the matrix metalloproteinases MMP9 and MMP13. Mechanistically, the combination therapy led to the downregulation of protein kinase B (pAKT) and RUNX2, along with upregulation of apoptotic markers, including caspase 8, caspase 3, and cleaved caspase 3, indicating a disruption of key survival pathways. These findings suggest that dual HDAC inhibition with Tas and PCI can potentiate doxo efficacy by enhancing apoptosis, inhibiting proliferation, and reducing metastatic potential, thus offering a promising strategy to overcome chemoresistance in osteosarcoma. Further preclinical and clinical studies are required to validate these therapeutic benefits. Full article

Background: the purpose of this study was to explore the effect of 10 weeks of yoga intervention on the mental health outcomes (stress, anxiety, and depression), quality of life, emotional regulation, and quality of sleep of medical students. Method: In the current experimental study, 220 medical students, with a mean age of 21.36 ± 2.20 years, participated in a 10-week yoga intervention at the University of Pécs. Data were collected before and after the intervention using the validated questionnaires DASS-21, WHOQOL-BREF, PSQI, and DERS. The distribution of data was checked using the Kolmogorov–Smirnov test. A paired sample T-test was used to compare the mean of the continuous variable. Stepwise linear regression was used to assess the association between mental health outcomes and quality-of-life variables. Results: The present study shows a significant reduction in (p < 0.001), depression (p < 0.001), and anxiety (p < 0.001) for participants, and overall quality of life (p < 0.001), quality of sleep (p < 0.001), and emotional regulation (p < 0.001) significantly improved after the intervention. The stepwise linear regression shows a strong association between higher levels of anxiety (β = 0.608, R² = 0.366) and depression (β = 0.608, R² = 0.392), with higher stress levels and improvement in environmental conditions being associated with a decrease in stress levels (β = −0.392, R² = 0.087). Conclusions: the current study shows that yoga significantly improved the mental health and well-being of medical students, improving quality of life, quality of sleep, and emotional regulation. Registered Clinical Trial: NCT06661603. Full article

Type 2 diabetes (T2D) and cardiovascular diseases (CVDs) are major public health challenges worldwide. Metabolomics, the exhaustive assessment of metabolites in biological systems, offers important insights regarding the metabolic disturbances related to these disorders. Recent advances toward the integration of metabolomics into clinical practice to facilitate the discovery of novel biomarkers that can improve the diagnosis, prognosis, and treatment of T2D and CVDs are discussed in this review. Metabolomics offers the potential to characterize the key metabolic alterations associated with disease pathophysiology and treatment. T2D is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms; therefore, the disease-causing pathways of T2D are not completely understood. Recent studies have identified several robust clusters of T2D variants representing biologically meaningful, distinct pathways, such as the beta cell and proinsulin cluster related to pancreatic insulin secretion, obesity, lipodystrophy, the liver/lipid cluster, glycemia, and blood pressure, and metabolic syndrome clusters representing different pathways causing insulin resistance. Regarding CVDs, recent studies have allowed the metabolomic profile to delineate pathways that contribute to atherosclerosis and heart failure, as well as to the development of targeted therapy. This review also covers the role of metabolomics in integrated metabolic genomics and other omics platforms to better understand disease mechanisms, along with the transition toward precision medicine. This review further investigates the use of metabolomics in multi-metabolite modeling to enhance risk prediction models for predicting the first occurrence of major adverse cardiovascular events among individuals with T2D, highlighting the value of such approaches in optimizing the preventive and therapeutic models used in clinical practice. Full article

Asthma and atherosclerosis are chronic conditions with distinct pathophysiologies, but overlapping inflammatory mechanisms that suggest a potential common regulatory framework. MicroRNAs (miRNAs), small non-coding RNA molecules that modulate gene expression post-transcriptionally, could be key players in linking these disorders. This review outlines how miRNAs contribute to the complex interplay between asthma and atherosclerosis, focusing on key miRNAs involved in inflammatory pathways, immune cell regulation and vascular remodeling. We discuss specific miRNAs, such as miR-155, miR-21 and miR-146a, which have been shown to modulate inflammatory cytokine production and T cell differentiation, impacting respiratory and cardiovascular health. The common miRNAs found in both asthma and atherosclerosis emphasize their role as potential biomarkers, but also as therapeutic targets. Understanding these molecular connections may unlock novel approaches for innovative, integrated treatment strategies that address both conditions and may significantly improve patient outcomes. Further research is needed to explore mechanistic pathways and validate the translational potential of miRNA-based interventions in preclinical and clinical settings. Full article

Background: Lymphopenia is associated with disease activity in adult patients with systemic lupus erythematosus (SLE), but no similar studies exist among children. Furthermore, lymphopenia has only been used as a parameter of disease activity in the SLE disease activity index (SLEDAI), but not as an independent marker. Objectives: This study aimed to ascertain lymphopenia as an independent marker related to disease activity in children with SLE. Methods: This was a retrospective cohort study on patients newly diagnosed with SLE. The data were collected from January 2009 to March 2017, including clinical manifestations, complete blood counts, anti-dsDNA, and Mexican-SLEDAI (MEX-SLEDAI) scores. Statistical analysis was performed using the Chi-square test, Student’s t-test, and ROC curve analysis. Results: A total of 103 patients, aged from 12 to 18 years, participated in the study. Of these, 58 patients (56.3%) exhibited lymphopenia. The most commonly observed clinical manifestations in the lymphopenia group included nephritis (72.4%), hypertension (24.1%), and leukopenia (36.2%), with p < 0.05. Furthermore, neuropsychiatric SLE was found exclusively in the lymphopenia group. A negative correlation was observed between lymphocyte counts and anti-dsDNA levels (r = −0.24), as well as between lymphocyte counts and the MEX-SLEDAI score (r = −0.63, with p < 0.05). The receiver operating characteristic (ROC) curve indicated that a lymphocyte count with a cut-off point of ≤1738/mm³ is significant for predicting anti-dsDNA reactivity. Conclusions: Lymphopenia is significantly correlated with higher anti-dsDNA levels and increased disease activity, potentially serving as an independent marker of disease activity in children with SLE. However, further research is needed. Full article

Cancer gene therapy is attracting considerable attention as a new treatment method for overcoming intractable cancers. CAR-T cell therapy has already achieved remarkable results, particularly for hematological tumors. Because CAR-T cells can increase within the body, they have the advantage of requiring only a single administration. In addition, CAR-T cell therapy targeting the CD19 antigen has been established for relapsed or refractory disease in young people with CD19-positive acute B-cell leukemia (B-acute lymphoblastic leukemia, B-ALL) and diffuse large B-cell lymphoma (DLBCL). In addition to CAR-T cell therapy, oncolytic viruses represent a promising approach for cancer treatment, with some already in clinical use and others being researched for their potential benefits. These viruses infect and kill cancer cells, triggering an immune response that helps the body recognize and fight cancer. Oncolytic virus therapy is a form of immunotherapy that uses modified viruses to target and destroy tumor cells while potentially stimulating antitumor immune responses. These viruses have shown promising activity in clinical trials, with some approved for specific cancers like melanoma. Research is ongoing to improve their efficacy, expand their use to other cancer types, and overcome the logistical challenges associated with their delivery. Gene therapy can potentially treat diseases caused by recessive gene disorders like cystic fibrosis, hemophilia, muscular dystrophy, and sickle cell anemia, as well as acquired genetic diseases, such as cancer and viral infections like acquired immunodeficiency syndrome (AIDS). Full article